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Gene chips used to distinguish ventilator-associated pneumonia from underlying critical illness
Date:2/12/2008

ivalent human genes could differentiate between pneumonia and inflammation in patients breathing with the assistance of ventilators. They narrowed their focus to 11 of 20 patients who developed pneumonia more than two days after having a breathing tube inserted. These patients had blood samples drawn at 48-hour intervals to determine whether changes in gene expression could monitor patients' response to treatment and their recovery. Most of the patients developed pneumonia within three to six days of being on a ventilator. None of them died.

The researchers used microarray analysis to study gene expression patterns in infection-fighting white blood cells contained in the blood samples. They found alterations in the activity of 85 genes some 24 to 72 hours before diagnosis of pneumonia by the physician attending in the ICU.

"This suggests that we could start patients on antibiotics earlier, say at the first change in these genomic vital signs, and we likely could significantly improve their ability to recover from pneumonia," Cobb says.

Many of the genes identified by the research team regulate specialized immune cells known as neutrophils. These cells dramatically increase in number as bacteria invade the body. "We found genes that control neutrophil activation were turned on, and that is consistent with someone developing a bacterial infection," Cobb explains. "We did not find neutrophil genes being activated in patients who did not have infection, even though they had fevers and high white blood cell counts."

Other genes of interest regulated messenger proteins called chemokines, which send signals recruiting immune cells to fight off infection.

The scientists confirmed the ability of their genomic analysis to diagnose infection and monitor recovery in a second small group of seven patients on mechanical ventilators, two of whom developed pneumonia. As the patients healed, alterations in the expression of the 85 genes di
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Contact: Caroline Arbanas
arbanasc@wustl.edu
314-286-0109
Washington University in St. Louis
Source:Eurekalert

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